Hypercharged Naturalness

We present an exceptional twin-Higgs model with the minimal symmetry structure for an exact implementation of twin parity along with custodial symmetry. Twin particles are mirrors of the Standard Model yet they carry hypercharge, while the photon is identified with its twin. We thoroughly explore the phenomenological signatures of hypercharged naturalness: long-lived charged particles, a colorless twin top with electric charge $2/3$ that once pair-produced, bounds via twin-color interactions and can annihilate to dileptons or a Higgs plus a photon or a $Z$, and glueballs produced from Higgs decays and twin-quarkonium annihilation that either decay displaced, or are stable on collider scales and eventually decay to diphotons. Prospects for detection of these signatures are also discussed.Comment: 37 pages, 7 figure

Vasopressin-2 receptor antagonists in autosomal dominant polycystic kidney disease: from man to mouse and back

nephropathy, with an esti-mated prevalence of 1:1000. The disease is characterized by the development of multiple cysts from all nephron segments leading to the enlargement of both kidneys and replacement of normal parenchyma (see [1]). Change in total kidney volume over time is the strongest predictor of renal function decline in ADPKD [2]. Glomerular filtra-tion rate remains preserved up to the age of 40 years in most patients because glomerular hyperfiltration in functioning nephrons compensates for the ongoing loss of renal tissue, until end-stage renal failure ensues in>50 % of patients, usually in their fifth decade. Mutations in the PKD1 gene account for ~85 % of the affected families, whereas the remaining cases are caused by mutations in PKD2. PKD1 encodes polycystin-1, an integral membrane protein with a large extracellular domain that probably functions as a re-ceptor and/or an adhesion molecule, whereas PKD2 enco-des polycystin-2, a non-selective cation channel belonging to the family of transient receptor potential channels. The polycystins are located in the primary cilium and interact to form a mechanosensory complex that is involved in intra-cellular Ca21 homeostasis and various signalling pathways. Disruption of the complex leads to cyst development and enlargement resulting from tubular cell proliferation and transepithelial fluid secretion. The progressive understand-ing of these pathways has led to spectacular advances in the prospective treatment for ADPKD, including the blockade of vasopressin 2 receptor (V2R) to decrease the intracellu-lar level of 3#-5#-cyclic adenosine monophosphate (cAMP) in cyst-lining tubular cells [1]

Runaway Relaxion from Finite Density

Finite density effects can destabilize the metastable vacua in relaxion models. Focusing on stars as nucleation seeds, we derive the conditions that lead to the formation and runaway of a relaxion bubble of a lower energy minimum than in vacuum. The resulting late-time phase transition in the universe allows us to set new constraints on the parameter space of relaxion models. We also find that similar instabilities can be triggered by the large electromagnetic fields around rotating neutron stars.Comment: 30 pages, 5 figures and several appendice

The Present and Future of Four Top Operators

We study the phenomenology of a strongly-interacting top quark at future hadron and lepton colliders, showing that the characteristic four-top contact operators give rise to the most significant effects. We demonstrate the extraordinary potential of a 100 TeV proton-proton collider to directly test such non-standard interactions in four-top production, a process that we thoroughly analyze in the same-sign dilepton and trilepton channels, and explore in the fully hadronic channel. Furthermore, high-energy electron-positron colliders, such as CLIC or the ILC, are shown to exhibit an indirect yet remarkable sensitivity to four-top operators, since these constitute, via renormalization group evolution, the leading new-physics deformations in top-quark pair production. We investigate the impact of our results on the parameter space of composite Higgs models with a strongly-coupled (right-handed) top quark, finding that four-top probes provide the best sensitivity on the compositeness scale at the future energy frontier. In addition, we investigate mild yet persisting LHC excesses in multilepton plus jets final states, showing that they can be consistently described in the effective field theory of such a new-physics scenario.Comment: 27 pages + references, 11 figures, 5 tables. v2: slight modification of title, minor additions to discussion (including HL-LHC projection), references added, results unchanged; version published in JHE

White dwarfs as a probe of light QCD axions

We study the effects of light QCD axions on the stellar configuration of white dwarfs. At finite baryon density, the non-derivative coupling of the axion to nucleons displaces the axion from its in-vacuum minimum which implies a reduction of the nucleon mass. This dramatically alters the composition of stellar remnants. In particular, the modifications of the mass-radius relationship of white dwarfs allow us to probe large regions of unexplored axion parameter space without requiring it to be a significant fraction of dark matter.Comment: 6 pages, 3 figure

Dual mTOR/PI3K inhibition limits PI3K-dependent pathways activated upon mTOR inhibition in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of kidney cysts leading to kidney failure in adulthood. Inhibition of mammalian target of rapamycin (mTOR) slows polycystic kidney disease (PKD) progression in animal models, but randomized controlled trials failed to prove efficacy of mTOR inhibitor treatment. Here, we demonstrate that treatment with mTOR inhibitors result in the removal of negative feedback loops and up-regulates pro-proliferative phosphatidylinositol 3-kinase (PI3K)-Akt and PI3K-extracellular signal-regulated kinase (ERK) signaling in rat and mouse PKD models. Dual mTOR/PI3K inhibition with NVP-BEZ235 abrogated these pro-proliferative signals and normalized kidney morphology and function by blocking proliferation and fibrosis. Our findings suggest that multi-target PI3K/mTOR inhibition may represent a potential treatment for ADPKD

Effective control of persistent hyperparathyroidism with cinacalcet in renal allograft recipients

Background. Cinacalcet rapidly normalizes serum calcium and reduces intact parathyroid hormone (PTH) levels in renal transplant patients with hypercalcaemia and persistent hyperparathyroidism. The aim of this study is to evaluate the 6 months efficacy of cinacalcet and the effect of cinacalcet withdrawal on serum calcium and PTH in such patients. Furthermore, the impact of cinacalcet on bone turnover and quality of life was assessed. Methods. Twelve renal allograft recipients with hypercalcaemia due to persistent hyperparathyroidism were treated with cinacalcet for 26 weeks. Cinacalcet was then withdrawn to check for recurrence of hypercalcaemia. Results. Cinacalcet maintained normocalcaemia in all patients from week 4 to 26, and PTH significantly decreased and remained suppressed. Serum phosphate increased, whereas the serum calcium-phosphate product remained unchanged. The excretion of calcium and phosphate in the 24 h urine had tendency to decrease. After cinacalcet was withdrawn, hypercalcaemia recurred rapidly and PTH increased to baseline values. Renal function remained stable, proteinuria was unchanged and no allograft rejection was observed. During treatment with cinacalcet, total and bone-specific alkaline phosphatase increased, whereas the urinary deoxypyridinoline-creatinine ratio did not change significantly, suggesting enhanced bone formation. Quality of life assessed at weeks 10 and 26 remained unchanged compared with baseline. Conclusions. In conclusion, continued treatment with cinacalcet is required to maintain long-term normocalcaemia and to suppress the enhanced PTH production in renal transplant recipients with persistent hyperparathyroidis

Long-term effect of coffee consumption on autosomal dominant polycystic kidneys disease progression: results from the Suisse ADPKD, a Prospective Longitudinal Cohort Study

BACKGROUND Previous in vitro experiments of human polycystic kidney disease (PKD) cells reported that caffeine is a risk factor for the promotion of cyst enlargement in patients with autosomal dominant PKD (ADPKD). The relentless progression of ADPKD inclines the majority of physicians to advocate minimization of caffeine consumption despite the absence of clinical data supporting such a recommendation so far. This is the first clinical study to assess prospectively the association between coffee consumption and disease progression in a longitudinal ADPKD cohort. METHODS Information on coffee consumption and disease progression was collected at each follow-up visit using standardized measurement methods. The main model for the outcomes, kidney size (height-adjusted total kidney volume, htTKV) and kidney function (estimated glomerular filtration rate, eGFR), was a linear mixed model. Patients entered the on-going Swiss ADPKD study between 2006 and June 2014 and had at least 1 visit every year. The sample size of the study population was 151 with a median follow-up of 4 visits per patient and a median follow-up time of 4.38 years. RESULTS After multivariate adjustment for age, smoking, hypertension, sex, body mass index and an interaction term (coffee*visit), coffee drinkers did not have a statistically significantly different kidney size compared to non-coffee drinkers (difference of -33.03 cm3 height adjusted TKV, 95% confidence interval (CI) from -72.41 to 6.34, p = 0.10). After the same adjustment, there was no statistically significant difference in eGFR between coffee and non-coffee drinkers (2.03 ml/min/1.73 m2, 95% CI from -0.31 to 4.31, p = 0.089). CONCLUSION Data derived from our prospective longitudinal study do not confirm that drinking coffee is a risk factor for ADPKD progression